Tibiofemoral knee osteoarthritis progresses symmetrically by knee compartment in the GOGO cohort.

Objective: To evaluate the degree of symmetry of knee osteoarthritis (OA) structural severity and progression of participants with a mean follow-up time of 3.8 years. Design: Participants from the Genetics of Generalized Osteoarthritis (GOGO) study (n = 705) were selected on the basis of radiographic evidence of OA in at least 1 knee, availability of radiographs at baseline and follow-up, and no history of prior knee injury or surgery. Incidence and progression of osteoarthritis were determined by radiographic Kellgren-Lawrence (KL) grade; compartmental OA progression was determined by change in joint space width of lateral and medial tibiofemoral compartments. Total OA progression was the sum of change in KL grade of both knees. Results: Compared with left knees, right knees had more severe KL grades at baseline (p = 0.0002) and follow-up (p = 0.0004), McNemar's χ2 = 34.16 and 26.08, respectively; however, both knees progressed similarly (p = 0.121, McNemar's χ2 = 10.09). Compartmental changes were symmetric across knees: medial r = 0.287, p = 0.0002; lateral r = 0.593, p = 0.0002. Change in joint space width in the medial compartment was negatively correlated with change in the lateral compartment of the same knee (left knees: r = -0.293, p = 0.021; right knees: r = -0.195, p = 0.0002). Conclusions: Although right knees tended to have more severe OA at both baseline and follow-up, radiographic progression did not differ by knee and compartmental progression correlated across knees. Given this trend in generalized OA, the risk of progression for both knees should be considered, even if only one knee has radiographic OA at baseline.

Knee osteoarthritis and time-to all-cause mortality in six community-based cohorts: an international meta-analysis of individual participant-level data.

BACKGROUND: Osteoarthritis (OA) is a chronic joint disease, with increasing global burden of disability and healthcare utilisation. Recent meta-analyses have shown a range of effects of OA on mortality, reflecting different OA definitions and study methods. We seek to overcome limitations introduced when using aggregate results by gathering individual participant-level data (IPD) from international observational studies and standardising methods to determine the association of knee OA with mortality in the general population. METHODS: Seven community-based cohorts were identified containing knee OA-related pain, radiographs, and time-to-mortality, six of which were available for analysis. A two-stage IPD meta-analysis framework was applied: (1) Cox proportional hazard models assessed time-to-mortality of participants with radiographic OA (ROA), OA-related pain (POA), and a combination of pain and ROA (PROA) against pain and ROA-free participants; (2) hazard ratios (HR) were then pooled using the Hartung-Knapp modification for random-effects meta-analysis. FINDINGS: 10,723 participants in six cohorts from four countries were included in the analyses. Multivariable models (adjusting for age, sex, race, BMI, smoking, alcohol consumption, cardiovascular disease, and diabetes) showed a pooled HR, compared to pain and ROA-free participants, of 1.03 (0.83, 1.28) for ROA, 1.35 (1.12, 1.63) for POA, and 1.37 (1.22, 1.54) for PROA. DISCUSSION: Participants with POA or PROA had a 35-37% increased association with reduced time-to-mortality, independent of confounders. ROA showed no association with mortality, suggesting that OA-related knee pain may be driving the association with time-to-mortality. FUNDING: Versus Arthritis Centre for Sport, Exercise and Osteoarthritis and Osteoarthritis Research Society International.

Polypharmacy and Incident Frailty in a Longitudinal Community-Based Cohort Study.

OBJECTIVES: Polypharmacy may affect frailty, a common and costly condition among older adults. Frailty prevalence is elevated among racial/ethnic minorities and persons living in the US South, and research is needed to inform future pharmacologic interventions in these populations. Our aim was to quantify the prevalence of frailty and polypharmacy, and to estimate the association between polypharmacy and incident frailty. DESIGN: Prospective cohort study. SETTING: A community-based cohort study of adults residing in Johnston County, North Carolina. PARTICIPANTS: White and African American adults aged 50 to 95 years (n=1697). MEASUREMENTS: At each study visit, all prescription and over-the-counter medications were recorded. We calculated annual polypharmacy (5-9 medications) and excessive polypharmacy (≥10 medications) prevalence at the 2006-2010 visit (n = 1697) and operationalized the Fried frailty phenotype to describe prevalent and incident frailty at two consecutive visits (2006-2010 and 2013-2015). We estimated risk ratios (RRs) and 95% confidence intervals (CIs) for the association between polypharmacy and incident frailty using weighted log-binomial regression to account for measured confounding and attrition using inverse probability of treatment and attrition weights, respectively. RESULTS: At the 2006-2010 visit, 678 (41%) and 260 (16%) participants were exposed to polypharmacy and excessive polypharmacy, respectively. Overall, 353 (21%) participants and 180 (21%) participants were frail at the 2006-2010 and 2013-2015 visits, respectively. Frailty was more common among participants identifying as white, women, and having less educational attainment relative to those without these characteristics. Incident frailty at the 2013-2015 visit was 15% (mean follow-up = 5.5 years). Our results suggest that polypharmacy is positively associated with incident frailty (weighted RR = 1.4; 95% CI = .9-2.0), yet estimates are imprecise and should be interpreted with caution. CONCLUSION: Consistent with the current weight of evidence, our results suggest an association between polypharmacy and incident frailty. Prospective studies evaluating deprescribing interventions are needed to clarify whether reducing polypharmacy decreases frailty incidence. J Am Geriatr Soc 67:2482-2489, 2019.

Genome-wide meta-analysis of 158,000 individuals of European ancestry identifies three loci associated with chronic back pain.

Back pain is the #1 cause of years lived with disability worldwide, yet surprisingly little is known regarding the biology underlying this symptom. We conducted a genome-wide association study (GWAS) meta-analysis of chronic back pain (CBP). Adults of European ancestry were included from 15 cohorts in the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, and from the UK Biobank interim data release. CBP cases were defined as those reporting back pain present for ≥3-6 months; non-cases were included as comparisons ("controls"). Each cohort conducted genotyping using commercially available arrays followed by imputation. GWAS used logistic regression models with additive genetic effects, adjusting for age, sex, study-specific covariates, and population substructure. The threshold for genome-wide significance in the fixed-effect inverse-variance weighted meta-analysis was p<5×10(-8). Suggestive (p<5×10(-7)) and genome-wide significant (p<5×10(-8)) variants were carried forward for replication or further investigation in the remaining UK Biobank participants not included in the discovery sample. The discovery sample comprised 158,025 individuals, including 29,531 CBP cases. A genome-wide significant association was found for the intronic variant rs12310519 in SOX5 (OR 1.08, p = 7.2×10(-10)). This was subsequently replicated in 283,752 UK Biobank participants not included in the discovery sample, including 50,915 cases (OR 1.06, p = 5.3×10(-11)), and exceeded genome-wide significance in joint meta-analysis (OR 1.07, p = 4.5×10(-19)). We found suggestive associations at three other loci in the discovery sample, two of which exceeded genome-wide significance in joint meta-analysis: an intergenic variant, rs7833174, located between CCDC26 and GSDMC (OR 1.05, p = 4.4×10(-13)), and an intronic variant, rs4384683, in DCC (OR 0.97, p = 2.4×10(-10)). In this first reported meta-analysis of GWAS for CBP, we identified and replicated a genetic locus associated with CBP (SOX5). We also identified 2 other loci that reached genome-wide significance in a 2-stage joint meta-analysis (CCDC26/GSDMC and DCC).

Time between anterior cruciate ligament injury and reconstruction and cartilage metabolism six-months following reconstruction.

BACKGROUND: To determine the association between time from injury to ACL reconstruction (TimeInjury-ACLR) and biochemical markers of cartilage metabolism and inflammation six months following ACL reconstruction (ACLR). METHODS: Individuals with a unilateral ACL injury were enrolled at initial presentation in the orthopedic clinic; blood was collected six months following ACLR. Enzyme-linked immunosorbent assays were used to analyze the ratio of serum concentrations of type-II collagen breakdown (C2C) to synthesis (CPII), plasma matrix metalloproteinase-3 (MMP-3), interleukin-6 (IL-6), and serum aggrecan neoepitope (ARGS). We used separate linear regressions to assess associations between biochemical markers and TimeInjury-ACLR. RESULTS: Twenty-two participants (50% females, mean [SD], age 21.9 [4.5] years old; BMI 23.8 [2.6] kg/m2) completed the study. TimeInjury-ACLR ranged from nine to 67days (31.0 [14.4days]). Greater TimeInjury-ACLR predicted greater serum C2C:CPII ratios six months following ACLR (C2C:CPII=0.15 [0.02], R2=0.213, P=0.030). Males (R2=0.733, P=0.001) but not females (R2=0.030, P=0.609) demonstrated a significant association between greater C2C:CPII and TimeInjury-ACLR at the six-month follow-up exam. TimeInjury-ACLR did not associate with IL-6, MMP-3, or ARGS at six months. CONCLUSIONS: Greater time between injury and ACL reconstruction was associated with greater serum C2C:CPII six months following ACLR in males but not females, and IL-6, MMP-3, and ARGS levels were not associated with TimeInjury-ACLR in males or females. The time between ACL injury and ACLR may affect collagen metabolism in males and should be further investigated in a larger study along with other patient-relevant outcomes.

Associations Between Slower Walking Speed and T1ρ Magnetic Resonance Imaging of Femoral Cartilage Following Anterior Cruciate Ligament Reconstruction.

OBJECTIVE: To determine whether walking speed, collected at 6 and 12 months following anterior cruciate ligament reconstruction (ACLR), is associated with inter-extremity differences in proteoglycan density, measured via T1ρ magnetic resonance imaging, in tibiofemoral articular cartilage 12 months following ACLR. METHODS: Twenty-one individuals with a unilateral patellar-tendon autograft ACLR (10 women and 11 men, mean ± SD age 23.9 ± 2.7 years, mean ± SD body mass index 23.9 ± 2.7 kg/m2 ) were recruited for participation in this study. Walking speed was collected using 3-dimensional motion capture at 6 and 12 months following ACLR. The articular cartilage of the medial femoral condyle (MFC) and lateral femoral condyle and medial and lateral tibial condyles was manually segmented and subsectioned into 3 regions of interest (anterior, central, and posterior) based on the location of the meniscus in the sagittal plane. Inter-extremity mean T1ρ relaxation time ratios (T1ρ ACLR extremity / T1ρ contralateral extremity) were calculated and used for analysis. Pearson product-moment correlations were used to determine associations between walking speed and inter-extremity differences in T1ρ relaxation time ratios. RESULTS: Slower walking speed 6 months post-ACLR was significantly associated with higher T1ρ relaxation time ratios in the MFC of the ACLR extremity 12 months following ACLR (posterior MFC, r = -0.51, P = 0.02; central MFC, r = -0.47, P = 0.04). Similarly, slower walking speed at 12 months post-ACLR was significantly associated with higher T1ρ relaxation time ratios in the posterior MFC ACLR extremity (r = -0.47, P = 0.04) 12 months following ACLR. CONCLUSION: Slower walking speed at 6 and 12 months following ACLR may be associated with early proteoglycan density changes in medial femoral compartment cartilage health in the first 12 months following ACLR.

Certified Athletic Trainers' Knowledge and Perceptions of Posttraumatic Osteoarthritis After Knee Injury.

CONTEXT: Posttraumatic osteoarthritis (PTOA) is a specific phenotype of osteoarthritis (OA) that commonly develops after acute knee injury, such as anterior cruciate ligament (ACL) or meniscal injury (or both). Athletic trainers (ATs) are well positioned to educate patients and begin PTOA management during rehabilitation of the acute injury, yet it remains unknown if ATs currently prioritize long-term outcomes in patients with knee injury. OBJECTIVE: To investigate ATs' knowledge and perceptions of OA and its treatment after ACL injury, ACL reconstruction, or meniscal injury or surgery. DESIGN: Cross-sectional study. PATIENTS OR OTHER PARTICIPANTS: An online survey was administered to 2000 randomly sampled certified ATs. We assessed participants' perceptions of knee OA, the risk of PTOA after ACL or meniscal injury or surgery, and therapeutic management of knee OA. RESULTS: Of the 437 ATs who responded (21.9%), the majority (84.7%) correctly identified the definition of OA, and 60.3% indicated that they were aware of PTOA. A high percentage of ATs selected full meniscectomy (98.9%), meniscal tear (95.4%), ACL injury (90.2%), and partial meniscectomy (90.1%) as injuries that would increase the risk of developing OA. Athletic trainers rated undertaking strategies to prevent OA development in patients after ACL injury or reconstruction (73.8%) or meniscal injury or surgery (74.7%) as extremely or somewhat important. Explaining the risk of OA to patients with an ACL or meniscal injury was considered appropriate by 98.8% and 96.8% of respondents, respectively; yet a lower percentage reported that they actually explained these risks to patients after an ACL (70.8%) or meniscal injury (80.6%). CONCLUSIONS: Although 84.7% of ATs correctly identified the definition of OA, a lower percentage (60.3%) indicated awareness of PTOA. These results may reflect the need to guide ATs on how to educate patients regarding the long-term risks of ACL and meniscal injuries and how to implement strategies that may prevent PTOA.

Novel Genetic Variants for Cartilage Thickness and Hip Osteoarthritis.

Osteoarthritis is one of the most frequent and disabling diseases of the elderly. Only few genetic variants have been identified for osteoarthritis, which is partly due to large phenotype heterogeneity. To reduce heterogeneity, we here examined cartilage thickness, one of the structural components of joint health. We conducted a genome-wide association study of minimal joint space width (mJSW), a proxy for cartilage thickness, in a discovery set of 13,013 participants from five different cohorts and replication in 8,227 individuals from seven independent cohorts. We identified five genome-wide significant (GWS, P≤5·0×10-8) SNPs annotated to four distinct loci. In addition, we found two additional loci that were significantly replicated, but results of combined meta-analysis fell just below the genome wide significance threshold. The four novel associated genetic loci were located in/near TGFA (rs2862851), PIK3R1 (rs10471753), SLBP/FGFR3 (rs2236995), and TREH/DDX6 (rs496547), while the other two (DOT1L and SUPT3H/RUNX2) were previously identified. A systematic prioritization for underlying causal genes was performed using diverse lines of evidence. Exome sequencing data (n = 2,050 individuals) indicated that there were no rare exonic variants that could explain the identified associations. In addition, TGFA, FGFR3 and PIK3R1 were differentially expressed in OA cartilage lesions versus non-lesioned cartilage in the same individuals. In conclusion, we identified four novel loci (TGFA, PIK3R1, FGFR3 and TREH) and confirmed two loci known to be associated with cartilage thickness.The identified associations were not caused by rare exonic variants. This is the first report linking TGFA to human OA, which may serve as a new target for future therapies.

Racial differences in associations between baseline patterns of radiographic osteoarthritis and multiple definitions of progression of hip osteoarthritis: the Johnston County Osteoarthritis Project.

BACKGROUND: To identify baseline radiographic features that predict hip osteoarthritis (HOA) progression, and to explore differences in these associations by race. METHODS: Radiographs from the community-based Johnston County OA Project were scored using Kellgren-Lawrence (KL) grade and for presence and location of joint space narrowing (JSN), osteophytes, and subchondral changes. Associations between these features and HOA progression (increase of at least 1 KL grade, interval hip replacement, range of motion [ROM, a reduction of ≥10° in internal rotation], or disability [increase of ≥0.2 in Health Assessment Questionnaire scores], or Any of these) were assessed using logistic regression, adjusting for age, gender, race, hip injury, BMI, education, smoking and follow-up time, accounting for multiple comparisons. Race interactions were assessed and analyses stratified as indicated. RESULTS: The sample (n = 1,422) included 40 % men and 26 % African American (AA) participants, with mean age 61 years and BMI 29 kg/m(2). The baseline frequency of radiographic hip OA (RHOA) between Caucasians and AAs was similar (23 %), although some radiographic features differed. AAs were more likely to have progression defined by ROM or disability or Any progression; Caucasians were more likely to have RHOA progression. JSN, subchondral sclerosis, and medial osteophytes were associated with increased RHOA progression overall; JSN was associated with disability progression only in AAs, while lateral osteophytes were associated with ROM progression only in Caucasians. CONCLUSIONS: AAs and Caucasians exhibited differences in the radiographic presentation and progression patterns of HOA, with AAs reporting progressive pain and disability, while Caucasians had more RHOA progression.

Low-grade inflammation in symptomatic knee osteoarthritis: prognostic value of inflammatory plasma lipids and peripheral blood leukocyte biomarkers.

OBJECTIVE: Inflammatory mediators, such as prostaglandin E2 (PGE2 ) and interleukin-1ß (IL-1ß), are produced by osteoarthritic (OA) joint tissue, where they may contribute to disease pathogenesis. We undertook the present study to examine whether inflammation, evidenced in plasma and peripheral blood leukocytes (PBLs), reflects the presence, progression, or specific symptoms of symptomatic knee OA. METHODS: Patients with symptomatic knee OA were enrolled in a 24-month prospective study of radiographic progression. Standardized knee radiographs were obtained at baseline and 24 months. At baseline, levels of the plasma lipids PGE2 and 15-hydroxyeicosatetraenoic acid (15-HETE) were measured, and transcriptome analysis of PBLs was performed by microarray and quantitative polymerase chain reaction. RESULTS: Baseline PGE2 synthase (PGES) levels determined by PBL microarray gene expression and plasma PGE2 levels distinguished patients with symptomatic knee OA from non-OA controls (area under the receiver operating characteristic curve [AUC] 0.87 and 0.89, respectively, P < 0.0001). Baseline plasma 15-HETE levels were significantly elevated in patients with symptomatic knee OA versus non-OA controls (P < 0.0195). In the 146 patients who completed the 24-month study, elevated baseline expression of IL-1ß, tumor necrosis factor α, and cyclooxygenase 2 (COX-2) messenger RNA in PBLs predicted higher risk of radiographic progression as evidenced by joint space narrowing (JSN). In a multivariate model, AUC point estimates of models containing COX-2 in combination with demographic traits overlapped the confidence interval of the base model in 2 of the 3 JSN outcome measures (JSN >0.0 mm, JSN >0.2 mm, and JSN >0.5 mm; AUC 0.62-0.67). CONCLUSION: The inflammatory plasma lipid biomarkers PGE2 and 15-HETE identify patients with symptomatic knee OA, and the PBL inflammatory transcriptome identifies a subset of patients with symptomatic knee OA who are at increased risk of radiographic progression. These findings may reflect low-grade inflammation in OA and may be useful as diagnostic and prognostic biomarkers in clinical development of disease-modifying OA drugs.

The Prevalence of Neck and Shoulder Symptoms and Associations with Comorbidities and Disability: The Johnston County Osteoarthritis Project.

OBJECTIVES: Neck and shoulder pain are common but underreported by older people, raising important questions of frequency, medical comorbidities, gender and racial disparities and functional impact associated with neck and shoulder symptoms in elders, which we examined in this analysis. METHODS: We performed a cross-sectional analysis in the community-based Johnston County Osteoarthritis Project, a cohort that is representative of the U.S. population, utilizing data from 1672 participants with a mean age of 68 years; 69% were white and 68% were women. Trained staff obtained data on participant-reported: symptoms, comorbidities, depression, and functional status; and performance-based functional assessments. Regression models of neck and shoulder symptoms and functional measures were adjusted for age, sex, race, and body mass index, and additionally for other joint symptoms and comorbidities. RESULTS: Symptoms of neck (8%), shoulder (13%) or both (13%) were reported by participants. Neck symptoms were most frequently reported by White women; shoulder symptoms were evenly distributed among race and gender subgroups. Neck and shoulder symptoms were associated with cancer, diabetes mellitus, depression, and lung, cardiovascular, and other musculoskeletal problems, as well as pain, aching or stiffness at other sites, and independently with self-reported and performance -based functional measures. CONCLUSIONS: These findings suggest that primary health care providers should inquire about neck and shoulder symptoms and address potential underlying causes to improve functional status and decrease disability in older people.

Associations between biomarkers of joint metabolism, hand osteoarthritis, and hand pain and function: the Johnston County Osteoarthritis Project.

OBJECTIVE: To determine the associations between joint metabolism biomarkers and hand radiographic osteoarthritis [(rOA), based on Kellgren Lawrence (KL) grade ≥ 2], symptoms, and function. METHODS: Cross-sectional data were available for 663 participants (mean age 63 yrs, 63% white, 49% women). Three definitions of hand rOA were considered: (1) a composite measure involving at least 3 hand joints distributed bilaterally with 2 of 3 in the same joint group, including ≥ 1 distal interphalangeal joint, without metacarpophalangeal (MCP) swelling; (2) rOA in at least 1 joint of a group; and (3) number of joints with KL ≥ 2. We assessed hand symptoms and the 15-item Australian Canadian Hand Osteoarthritis Index (AUSCAN; Likert format). We measured serum cartilage oligomeric matrix protein (sCOMP), hyaluronic acid (sHA), carboxy-terminal propeptide of type II collagen, type II collagen degradation product, urinary C-terminal crosslinked telopeptide of type II collagen, and urinary N-terminal crosslinked telopeptide. Linear regression models were performed to assess associations between each biomarker with hand rOA, AUSCAN, and symptoms, adjusting for age, sex, race, current smoking/drinking status, body mass index, and hip and knee rOA. RESULTS: In adjusted analyses, MCP (p < 0.0001) and carpometacarpal rOA (p = 0.003), and a higher number of hand joints with rOA (p = 0.009), were associated with higher levels of sHA. Positive associations were seen between AUSCAN and hand symptoms and levels of sCOMP (p ≤ 0.003) and sHA (p ≤ 0.048). CONCLUSION: Hand symptoms and higher AUSCAN scores were independently associated with higher levels of both sCOMP and sHA; hand rOA was associated only with sHA levels.

A systematic review of recommendations and guidelines for the management of osteoarthritis: The chronic osteoarthritis management initiative of the U.S. bone and joint initiative.

PURPOSE: Although a number of osteoarthritis (OA) management guidelines exist, uptake has been suboptimal. Our aim was to review and critically evaluate existing OA management guidelines to better understand potential issues and barriers. METHODS: A systematic review of the literature in MEDLINE published from January 1, 2000 to April 1, 2013 was performed and supplemented by bibliographic reviews, following PRISMA guidelines and a written protocol. Following initial title and abstract screening, 2 authors independently reviewed full-text articles; a third settled disagreements. Two independent reviewers extracted data into a standardized form. Two authors independently assessed guideline quality using the AGREE II instrument; three generated summary recommendations based on the extracted guideline data. RESULTS: Overall, 16 articles were included in the final review. There was broad agreement on recommendations by the various organizations. For non-pharmacologic modalities, education/self-management, exercise, weight loss if overweight, walking aids as indicated, and thermal modalities were widely recommended. For appropriate patients, joint replacement was recommended; arthroscopy with debridement was not recommended for symptomatic knee OA. Pharmacologic modalities most recommended included acetaminophen/paracetamol (first line) and NSAIDs (topical or oral, second line). Intra-articular corticosteroids were generally recommended for hip and knee OA. Controversy remains about the use of acupuncture, knee braces, heel wedges, intra-articular hyaluronans, and glucosamine/chondroitin. CONCLUSIONS: The relative agreement on many OA management recommendations across organizations indicates a problem with dissemination and implementation rather than a lack of quality guidelines. Future efforts should focus on optimizing implementation in primary care settings, where the majority of OA care occurs.

Distributions and determinants of mercury concentrations in toenails among American young adults: the CARDIA Trace Element Study.

Since data on mercury (Hg) levels in Caucasians and African Americans (AAs) of both genders are lacking, this study aims to present toenail Hg distributions and explore the potential determinants using data from the Coronary Artery Risk Development in Young Adults Trace Element Study. Data from 4,344 Americans, aged 20-32 in 1987, recruited from Oakland, Chicago, Minneapolis, and Birmingham were used to measure toenail Hg levels by instrumental neutron-activation method. The Hg distribution was described with selected percentiles and geometric means. Multivariable linear regression (MLR) was used to examine potential determinants of Hg levels within ethnicity-gender subgroups. The geometric mean of toenail Hg was 0.212 (95 % CI = 0.207-0.218) µg/g. Hg levels varied geographically with Oakland the highest [0.381 (0.367-0.395) µg/g] and Minneapolis the lowest [0.140 (0.134-0.147) µg/g]. MLR analyses showed that male gender and AA ethnicity were negatively associated with toenail Hg levels, and that age, living in Oakland city, education level, alcohol consumption, and total fish intake were positively associated with toenail Hg concentrations within each ethnicity-gender subgroup. Current smokers were found to have higher Hg only in AA men. This study suggested age, gender, ethnicity, study center, alcohol, education level, and fish consumption consistently predict toenail Hg levels. As fish consumption was the key determinant, avoiding certain types of fish that have relatively high Hg levels may be crucial in reducing Hg intake.

Association of slower walking speed with incident knee osteoarthritis-related outcomes.

OBJECTIVE: To determine whether slower walking speed was associated with an increased risk of incident hip and knee osteoarthritis (OA)-related outcomes. METHODS: After providing informed consent, community-dwelling participants in the Johnston County Osteoarthritis Project completed 2 home-based interviews and an additional clinic visit for radiographic and physical evaluation. One thousand eight hundred fifty-eight noninstitutionalized residents ages ≥ 45 years living for at least 1 year in 1 of 6 townships in Johnston County, North Carolina, completed the study's questionnaires and clinical examinations at baseline and at followup testing. Walking time was assessed using a manual stopwatch in 2 trials over an 8-foot distance, and walking speed was calculated as the average of both trials. For the hip and knee, we examined 3 outcomes per joint site: radiographic OA (weight-bearing anteroposterior knee radiographs, supine anteroposterior pelvic radiographs of the hip), chronic joint symptoms, and symptomatic OA. Covariates included age, sex, race, education, marital status, body mass index, number of self-reported chronic conditions diagnosed by a health care provider, number of prescriptions, depressive symptoms, self-rated health, number of lower body functional limitations, smoking, and physical activity. RESULTS: Faster walking speed was consistently associated with a lower incidence of radiographic (adjusted odds ratio [OR] 0.88, 95% confidence interval [95% CI] 0.79-0.97) and symptomatic knee OA (adjusted OR 0.84, 95% CI 0.75-0.95); slower walking speed was associated with a greater incidence of these outcomes across a broad range of different clinical and radiographic OA outcomes. CONCLUSION: Slower walking speed may be a marker for incident knee OA, but other studies must confirm this finding.

Associations of educational attainment, occupation and community poverty with knee osteoarthritis in the Johnston County (North Carolina) osteoarthritis project.

INTRODUCTION: The purpose of this study was to examine data from the Johnston County Osteoarthritis (OA) Project for independent associations of educational attainment, occupation and community poverty with tibiofemoral knee OA. METHODS: A cross-sectional analysis was conducted on 3,591 individuals (66% Caucasian and 34% African American). Educational attainment (< 12 years or ≥12 years), occupation (non-managerial or not), and census block group household poverty rate (< 12%, 12 to 25%, > 25%) were examined separately and together in logistic models adjusting for covariates of age, gender, race, body mass index (BMI), smoking, knee injury and occupational activity score. Outcomes were presence of radiographic knee OA (rOA), symptomatic knee OA (sxOA), bilateral rOA and bilateral sxOA. RESULTS: When all three socioeconomic status (SES) variables were analyzed simultaneously, low educational attainment was significantly associated with rOA (odds ratio (OR) = 1.44, 95% confidence interval (CI) 1.20, 1.73), bilateral rOA (OR = 1.43, 95% CI 1.13, 1.81), and sxOA (OR = 1.66, 95% CI 1.34, 2.06), after adjusting for covariates. Independently, living in a community of high household poverty rate was associated with rOA (OR = 1.83, 95% CI 1.43, 2.36), bilateral rOA (OR = 1.56, 95% CI 1.12, 2.16), and sxOA (OR = 1.36, 95% CI 1.00, 1.83). Occupation had no significant independent association beyond educational attainment and community poverty. CONCLUSIONS: Both educational attainment and community SES were independently associated with knee OA after adjusting for primary risk factors for knee OA.

Whole blood lead levels are associated with biomarkers of joint tissue metabolism in African American and white men and women: the Johnston County Osteoarthritis Project.

PURPOSE: To examine associations between biomarkers of joint tissue metabolism and whole blood lead (Pb), separately for men and women in an African American and Caucasian population, which may reflect an underlying pathology. METHODS: Participants in the Johnston County Osteoarthritis Project Metals Exposure Sub-Study (329 men and 342 women) underwent assessment of whole blood Pb and biochemical biomarkers of joint tissue metabolism. Urinary cross-linked N telopeptide of type I collagen (uNTX-I) and C-telopeptide fragments of type II collagen (uCTX-II), serum cleavage neoepitope of type II collagen (C2C), serum type II procollagen synthesis C-propeptide (CPII), and serum hyaluronic acid (HA) were measured using commercially available kits; the ratio of [C2C:CPII] was calculated. Serum cartilage oligomeric matrix protein (COMP) was measured by an in-house assay. Multiple linear regression models were used to examine associations between continuous blood Pb and biomarker outcomes, adjusted for age, race, current smoking status, and body mass index. Results are reported as estimated change in biomarker level for a 5-unit change in Pb level. RESULTS: The median Pb level among men and women was 2.2 and 1.9µg/dL, respectively. Correlations were noted between Pb levels and the biomarkers uNTX-I, uCTX-II, and COMP in women, and between Pb and uCTX-II, COMP, CPII, and the ratio [C2C:CPII] in men. In adjusted models among women, a 5-unit increase in blood Pb level was associated with a 28% increase in uCTX-II and a 45% increase in uNTX-I levels (uCTX-II: 1.28 [95% CI: 1.04-1.58], uNTX-I: 1.45 [95% CI:1.21-1.74]). Among men, levels of Pb and COMP showed a borderline positive association (8% increase in COMP for a 5-unit change in Pb: 1.08 [95% CI: 1.00-1.18]); no other associations were significant after adjustment. CONCLUSIONS: Based upon known biomarker origins, the novel associations between blood Pb and biomarkers appear to be primarily reflective of relationships to bone and calcified cartilage turnover among women and cartilage metabolism among men, suggesting a potential gender-specific effect of Pb on joint tissue metabolism that may be relevant to osteoarthritis.

OARSI/OMERACT initiative to define states of severity and indication for joint replacement in hip and knee osteoarthritis. An OMERACT 10 Special Interest Group.

OBJECTIVE: To define pain and physical function cutpoints that would, coupled with structural severity, define a surrogate measure of "need for joint replacement surgery," for use as an outcome measure for potential structure-modifying interventions for osteoarthritis (OA). METHODS: New scores were developed for pain and physical function in knee and hip OA. A cross-sectional international study in 1909 patients was conducted to define data-driven cutpoints corresponding to the orthopedic surgeons' indication for joint replacement. A post hoc analysis of 8 randomized clinical trials (1379 patients) evaluated the prevalence and validity of cutpoints, among patients with symptomatic hip/knee OA. RESULTS: In the international cross-sectional study, there was substantial overlap in symptom levels between patients with and patients without indication for joint replacement; indeed, it was not possible to determine cutpoints for pain and function defining this indication. The post hoc analysis of trial data showed that the prevalence of cases that combined radiological progression, high level of pain, and high degree of function impairment was low (2%-12%). The most discriminatory cutpoint to define an indication for joint replacement was found to be [pain (0-100) + physical function (0-100) > 80]. CONCLUSION: These results do not support a specific level of pain or function that defines an indication for joint replacement. However, a tentative cutpoint for pain and physical function levels is proposed for further evaluation. Potentially, this symptom level, coupled with radiographic progression, could be used to define "nonresponders" to disease-modifying drugs in OA clinical trials.

Whole blood lead levels are associated with radiographic and symptomatic knee osteoarthritis: a cross-sectional analysis in the Johnston County Osteoarthritis Project.

INTRODUCTION: Lead (Pb) is known to affect bone, and recent evidence suggests that it has effects on cartilage as well. As osteoarthritis (OA) is a highly prevalent disease affecting bone and cartilage, we undertook the present analysis to determine whether whole blood Pb levels are associated with radiographic and symptomatic OA (rOA and sxOA, respectively) of the knee. METHODS: The analysis was conducted using cross-sectional data from the Johnston County Osteoarthritis Project, a rural, population-based study, including whole blood Pb levels, bilateral posteroanterior weight-bearing knee radiography and knee symptom data. rOA assessment included joint-based presence (Kellgren-Lawrence (K-L) grade 2 or higher) and severity (none, K-L grade 0 or 1; mild, K-L grade 2; moderate or severe, K-L grade 3 or 4), as well as person-based laterality (unilateral or bilateral). SxOA was deemed present (joint-based) in a knee on the basis of K-L grade 2 or higher with symptoms, with symptoms rated based on severity (0, rOA without symptoms; 1, rOA with mild symptoms; 2, rOA with moderate or severe symptoms) and in person-based analyses was either unilateral or bilateral. Generalized logit or proportional odds regression models were used to examine associations between the knee OA status variables and natural log-transformed blood Pb (ln Pb), continuously and in quartiles, controlling for age, race, sex, body mass index (BMI), smoking and alcohol drinking. RESULTS: Those individuals with whole blood Pb data (N = 1,669) had a mean (±SD) age of 65.4 (±11.0) years and a mean BMI of 31.2 (±7.1) kg/m2, including 66.6% women and 35.4% African-Americans, with a median blood Pb level of 1.8 µg/dl (range, 0.3 to 42.0 µg/dl). In joint-based analyses, for every 1-U increase in ln Pb, the odds of prevalent knee rOA were 20% higher (aOR, 1.20; 95% CI, 1.01 to 1.44), while the odds of more severe rOA were 26% higher (aOR, 1.26; 95% CI, 1.05 to 1.50, under proportional odds). In person-based analyses, the odds of bilateral rOA were 32% higher for each 1-U increase in ln Pb (aOR, 1.32; 95% CI, 1.03 to 1.70). Similarly for knee sxOA, for each 1-U increase in ln Pb, the odds of having sxOA were 16% higher, the odds of having more severe symptoms were 17% higher and the odds of having bilateral knee symptoms were 25% higher. Similar findings were obtained with regard to ln Pb in quartiles. CONCLUSIONS: Increases in the prevalence and severity measures for both radiographically and symptomatically confirmed knee OA (although statistically significant only for rOA) were observed with increasing levels of blood Pb, suggesting that Pb may be a potentially modifiable environmental risk factor for OA.